Statins cause a moderate increase in new diagnoses of diabetes consistent with a slight uptick in glycaemia, albeit mainly among those already close to biochemical diagnostic thresholds, a review has concluded.
Based on 23 trials totalling more than 150,000 participants, the findings are reassuring overall but highlight the need for diabetes screening of higher-risk patients on statin therapy, according to the researchers.
They stress that, importantly, the diabetes-related risks arising from the small changes in glycaemia resulting from statin therapy are “greatly outweighed” by their cardiovascular benefits.
Moreover, any theoretical adverse effects of statins on cardiovascular risk identified in the review potentially arising from these increases (or, indeed, from any other mechanism) were already accounted for in the overall reduction in cardiovascular risk seen with statin therapy in the included trials.
The review included 19 trials comparing statin versus placebo (123,940 participants and a median of 4.3-year follow-up) and four comparing more versus less intensive statin therapy (30,774 participants followed a median of 4.9 years).
Findings were that, compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes.
Meanwhile, allocation to high-intensity statin therapy resulted in a 36% proportional increase, the reviewers reported in The Lancet Diabetes & Endocrinology (link here).
These increases persisted when biochemically determined diagnoses of diabetes were excluded, they wrote.
Overall, the rate ratios were consistent with a small increase in glycaemia, with mean glucose rising by 0.004 mmol/L in those receiving statins regardless of intensity. Mean HbA1c increased by 0.06% with low-intensity or moderate-intensity statins and 0.08% with high-intensity statins.
“These effects were widely generalisable to the different types of participants studied and persisted while treatment continued,” the authors wrote.
But significantly, the bulk of new-onset diabetes diagnoses (62%) were among participants already in the top quartile baseline distribution for both measures, placing them close to the biochemical diagnostic threshold for diabetes, they said.
“Our findings also imply that, since the effect of statin therapy on measures of glycaemia within an individual is small (i.e., considerably smaller than the combined variation of within-individual and laboratory analytical variation), there is likely to be little clinical benefit in measuring glucose concentrations and HbA1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin,” the authors added.
“However, people should continue to be screened for diabetes and associated risk factors and have their glycaemic control monitored in accordance with current clinical guidelines.”
Among participants with baseline diabetes, the risk ratios for worsening glycaemia were 1.10 for low-intensity or moderate-intensity statin therapy and 1.24 for high-intensity statin therapy compared with placebo, the authors noted.
The authors concluded by stressing the mean changes in glycaemia were small, while the evidence of the beneficial effects on major vascular events provided reassurance about the net benefits of using statin therapy in individuals at increased risk of developing diabetes or who had already developed it.
“Among people without diabetes, statin therapy produces a dose-dependent increase in the rate of diagnosis of diabetes by inducing a very small increase in glycaemia,” they wrote.
“People are most at risk of exceeding the diagnostic threshold for diabetes due to statin therapy if their glycaemic control is close to the threshold before treatment.”
“The diabetes-related risks arising from the small changes in glycaemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration.”